This phase II trial studies how well dabrafenib with trametinib work after radiation therapy in treating patients with a type of genetic mutation (BRAF V600-mutant) and newly-diagnosed, high-grade glioma. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in helping to get rid of or shrinking tumors in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.
Name: Dabrafenib
Description: Given POType: DrugTreatment (radiation therapy, dabrafenib, trametinib)
Name: Dabrafenib Mesylate
Description: Given POType: DrugTreatment (radiation therapy, dabrafenib, trametinib)
Name: Radiation Therapy
Description: Undergo RTType: RadiationTreatment (radiation therapy, dabrafenib, trametinib)
Name: Trametinib
Description: Given POType: DrugTreatment (radiation therapy, dabrafenib, trametinib)
Name: Trametinib Dimethyl Sulfoxide
Description: Given POType: DrugTreatment (radiation therapy, dabrafenib, trametinib)
Description: The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.
Measure: Event-free survival (EFS) Time: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 yearsDescription: The OS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control.
Measure: Overall survival (OS) Time: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 yearsDescription: Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.
Measure: Incidence of adverse events Time: Up to 5 yearsSingle Group Assignment
There is one SNP
- Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 - Newly diagnosed high-grade glioma with BRAFV600-mutation - Negative results for H3 K27M by immunohistochemistry (IHC) - Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS) - Patients must have had histologic verification of a high-grade glioma diagnosis. --- K27M ---
Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma BRAF NP_004324.2:p.V600X Glioblastoma H3 K27M Negative Malignant Glioma WHO Grade III Glioma Glioblastoma Glioma Astrocytoma Ganglioglioma PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls. --- K27M ---
Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma BRAF NP_004324.2:p.V600X Glioblastoma H3 K27M Negative Malignant Glioma WHO Grade III Glioma Glioblastoma Glioma Astrocytoma Ganglioglioma PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls. --- K27M --- --- K27M ---
SECONDARY OBJECTIVES: I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAFV600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---
To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---